{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:53:32Z","timestamp":1790621612623,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL134791"],"award-info":[{"award-number":["HL134791"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL104025"],"award-info":[{"award-number":["HL104025"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,3]]},"abstract":"<jats:p>\n                    Cardiac ischemia is associated with arrhythmias; however, effective therapies are currently limited. The cardiac voltage-gated sodium channel \u03b1 subunit (\n                    <jats:italic>SCN5A<\/jats:italic>\n                    ), encoding the Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 current, plays a key role in the cardiac electrical conduction and arrhythmic risk. Here, we show that hypoxia reduces Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 through effects on a miR, miR-448. miR-448 expression is increased in ischemic cardiomyopathy. miR-448 has a conserved binding site in 3\u2032-UTR of\n                    <jats:italic>SCN5A<\/jats:italic>\n                    . miR-448 binding to this site suppressed\n                    <jats:italic>SCN5A<\/jats:italic>\n                    expression and sodium currents. Hypoxia-induced HIF-1\u03b1 and NF-\u03baB were major transcriptional regulators for\n                    <jats:italic>MIR448<\/jats:italic>\n                    . Moreover, hypoxia relieved\n                    <jats:italic>MIR448<\/jats:italic>\n                    transcriptional suppression by RE1 silencing transcription factor. Therefore, miR-448 inhibition reduced arrhythmic risk after myocardial infarction. Here, we show that ischemia drove miR-448 expression, reduced Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 current, and increased arrhythmic risk. Arrhythmic risk was improved by preventing Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 downregulation, suggesting a new approach to antiarrhythmic therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.140759","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T12:56:16Z","timestamp":1603803376000},"source":"Crossref","is-referenced-by-count":24,"title":["MIR448 antagomir reduces arrhythmic risk after myocardial infarction by upregulating the cardiac sodium channel"],"prefix":"10.1172","volume":"5","author":[{"given":"Gyeoung-Jin","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Samuel 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